Cortical Inhibition, Gamma-Aminobutyric Acid, and Major Depression: There Is Plenty of Smoke but Is There Fire?

Abstract

The pathophysiological processes underlying major depressive disorder (MDD) have remained elusive despite tremendous efforts and expenditures. For the past five decades, the focus of investigation has remained largely on neurochemical abnormalities within the monoaminergic neurotransmitter systems. However, slowly, over the last 30 years, evidence has accumulated suggesting that altered function of the amino acid neurotransmitter systems, especially the major inhibitory gamma-aminobutyric acid (GABA)ergic system, may contribute significantly to the pathophysiology and potentially successful treatment of the disorder ( 1 Sanacora G. Saricicek A. GABAergic contributions to the pathophysiology of depression and the mechanism of antidepressant action. CNS Neurol Disord Drug Targets. 2007; 6: 127-140 Crossref PubMed Scopus (107) Google Scholar ). The recent findings by Levinson et al. ( 2 Levinson A.J. Fitzgerald P.B. Favalli G. Blumberger D.M. Daigle M. Daskalakis Z.J. Evidence of Cortical Inhibitory Deficits in Major Depressive Disorder. Biol Psychiatry. 2010; 67: 458-464 Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar ) augment this growing body of literature by demonstrating specific neurophysiological effects that are likely related to GABAergic changes in the brains of some individuals suffering with MDD. Evidence of Cortical Inhibitory Deficits in Major Depressive DisorderBiological PsychiatryVol. 67Issue 5PreviewSeveral lines of evidence suggest that major depressive disorder is associated with deficits in γ-aminobutyric acid (GABA) inhibitory neurotransmission. Transcranial magnetic stimulation represents a noninvasive technique to measure cortical inhibition. In this study, we endeavored to measure cortical inhibition in medicated patients with treatment resistant major depressive disorder (TRD), unmedicated patients with major depressive disorder, and medicated euthymic patients with a history of major depressive disorder and compare them with healthy subjects. Full-Text PDF